P-element vectors are modified transposable elements widely used to make transgenic Drosophila. In general, insertion of P-element vectors is nonrandom, but exhibits a very broad specificity of target sites. During experiments to identify cis-acting regulatory elements of the Drosophila segmentation gene engrailed (en), we noticed that whenever a particular fragment of &n DNA was included within a P-element vector, the specificity for insertion sites was strikingly altered. In particular, P elements containing a small fragment of en regulatory DNA insert at a high frequency near genes expressed in stripes. How does this selective insertion occur? We favor a model whereby a protein(s) bound to the in fragment within the P element brings it to a particular region of the genome via protein-protein or protein-DNA interactions and enhances the probability of insertion within this region. This model presumes that the genes that are 'targeted" by such P elements share a co=on structure or location in the nucleus. Such selective insertion near a class of related genes by a transposon (or retrovirus) could dramatically influence the expression of the vector-encoded genes thereby contributing to its tissue-specificity. These experiments should give us insight into how some retroviruses may acquire tissue specificity.